A Novel 29-kDa Crystal Protein from<i>Bacillus thuringiensis</i>Induces Caspase Activation and Cell Death of Jurkat T Cells

Amano, Hiromi; Yamagiwa, Masashi; Akao, Tetsuyuki; Mizuki, Eiichi; Ohba, Michio; Sakai, Hiroshi

doi:10.1271/bbb.69.2063

Cited by 11 publications

(7 citation statements)

References 34 publications

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“…So far, some other parasporins have been shown to induce apoptosis in mammalian cancer cells [ 45 , 46 ]. However, we are the first to demonstrate the apoptotic effects of parasporin-2Aa1 (PS2Aa1).…”

Section: Discussionmentioning

confidence: 99%

“…Another 29 kDa parasporin from the B . thuringiensis A1519 strain induces mitochondrial apoptosis pathway in the Jurkat cells via caspase-3 and -9 cleavage and the release of cytochrome c from the mitochondria [ 45 ]. In a previous study, it was reported that HepG2 cells, treated with PS2Aa1, have shown a leakage of cytochrome C from mitochondria who was not consider at that time as an apoptotic event [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

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Parasporin-2 from a New Bacillus thuringiensis 4R2 Strain Induces Caspases Activation and Apoptosis in Human Cancer Cells

et al. 2015

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In previous studies, parasporin-2Aa1, originally isolated from Bacillus thuringiensis strain A1547, was shown to be cytotoxic against specific human cancer cells but the mechanisms of action were not studied. In the present study, we found that proteinase K activated parasporin-2Aa1 protein isolated from a novel B. thuringiensis strain, 4R2, was specifically cytotoxic to endometrial, colon, liver, cervix, breast and prostate cancer. It showed no toxicity against normal cells. Upon treatment with proteinase K-activated parasporin-2Aa1, morphological changes were observed and western blot analysis revealed the cleavage of poly (ADP-Ribose) polymerase, caspase-3 and caspase-9 in cancer cell lines exclusively, indicative of programmed cell death, apoptosis. Flow cytometry analyses,using propidium iodide and annexin V, as well as a caspases 3/7 assay confirmed apoptosis induction. Further analyses were performed to study survival pathways, including AKT, XIAP, ERK1/2 and PAR-4, a known inducer of apoptosis. These results indicate that parasporin-2Aa1 is a selective cytotoxic protein that induces apoptosis in various human cancer cell lines from diverse tissues.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Parasporin-2 from a New Bacillus thuringiensis 4R2 Strain Induces Caspases Activation and Apoptosis in Human Cancer Cells

et al. 2015

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“…Caspase activation was involved in apoptosis (Cohen, 1997;Ayala-Groeso et al 2002;Amano et al 2005;Denecker et al 2008;Pop and Salvesen 2009;Hyman andYuan 2012, 2012). The two classical apoptotic pathways are the intrinsic, or mitochondrial pathway, and the extrinsic pathway.…”

Section: Discussionmentioning

confidence: 99%

Caspase-8 Mediates Amyloid-β-induced Apoptosis in Differentiated PC12 Cells

et al. 2015

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The pathogenesis of Alzheimer's disease (AD) is very complex and there are currently no significant treatments for the disease. Caspase-8 is known to be involved in neuronal apoptosis. To explore a possible molecular mechanisms involved in AD pathology, this study investigated the effect of caspase-8 knockdown on amyloid-β 1-40 (Aβ1-40)-induced apoptosis in PC12 cells. The proliferation of PC12 cells was significantly inhibited in Aβ-treated cells, and a high fraction of the cells underwent apoptosis in a dose- and time-dependent manner. Transfection of caspase-8 small interfering RNA (siRNA) resulted in reduced apoptosis following Aβ1-40 treatment. The activation of caspase-3, caspase-8, and caspase-9 was stimulated by Aβ1-40, an effect that was also significantly reduced by caspase-8 siRNA. Knockdown of caspase-8 increased the phosphorylation of the signaling molecules AKT and ERK1/2 relative to cells treated with Aβ1-40 alone. Caspase-8 is an important effector molecule involved in apoptosis induced by Aβ1-40 and is likely involved in AD pathology. This study suggests that targeted inhibition of caspase-8 may be a new therapeutic for preventing neuronal apoptosis and inhibiting the progression of AD.

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“…On the other hand, it has been reported that the proteinase K-activated 29-kDa toxin from noninsecticidal B. thuringiensis strain A1519, which shows similar target cell specificities to parasporin-2, induces apoptosis of Jurkat cells in addition to cell swelling (24). Thus, parasporal B. thuringiensis toxins seem to induce cell death through individual processes.…”

Section: Discussionmentioning

confidence: 99%

Cytocidal Actions of Parasporin-2, an Anti-tumor Crystal Toxin from Bacillus thuringiensis

Kitada

Abe

Shimada

et al. 2006

Journal of Biological Chemistry

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Parasporin-2, a new crystal protein derived from noninsecticidal and nonhemolytic Bacillus thuringiensis, recognizes and kills human liver and colon cancer cells as well as some classes of human cultured cells. Here we report that a potent proteinase K-resistant parasporin-2 toxin shows specific binding to and a variety of cytocidal effects against human hepatocyte cancer cells. Cleavage of the N-terminal region of parasporin-2 was essential for the toxin activity, whereas C-terminal digestion was required for rapid cell injury. Protease-activated parasporin-2 induced remarkable morphological alterations, cell blebbing, cytoskeletal alterations, and mitochondrial and endoplasmic reticulum fragmentation. The plasma membrane permeability was increased immediately after the toxin treatment and most of the cytoplasmic proteins leaked from the cells, whereas mitochondrial and endoplasmic reticulum proteins remained in the intoxicated cells. Parasporin-2 selectively bound to cancer cells in slices of liver tumor tissues and susceptible human cultured cells and became localized in the plasma membrane until the cells were damaged. Thus, parasporin-2 acts as a cytolysin that permeabilizes the plasma membrane with target cell specificity and subsequently induces cell decay.

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A Novel 29-kDa Crystal Protein fromBacillus thuringiensisInduces Caspase Activation and Cell Death of Jurkat T Cells

Cited by 11 publications

References 34 publications

Parasporin-2 from a New Bacillus thuringiensis 4R2 Strain Induces Caspases Activation and Apoptosis in Human Cancer Cells

Parasporin-2 from a New Bacillus thuringiensis 4R2 Strain Induces Caspases Activation and Apoptosis in Human Cancer Cells

Caspase-8 Mediates Amyloid-β-induced Apoptosis in Differentiated PC12 Cells

Cytocidal Actions of Parasporin-2, an Anti-tumor Crystal Toxin from Bacillus thuringiensis

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